Evidence of the transient nature of the Th17 phenotype of CD4+CD161+ T cells in the synovial fluid of patients with juvenile idiopathic arthritis

Cosmi, Lorenzo; Cimaz, Rolando; Maggi, Laura; Santarlasci, Veronica; Capone, Manuela; Borriello, Francesco; Frosali, Francesca; Querci, Valentina; Simonini, Gabriele; Barra, Giusi; Piccinni, Marie‐Pierre; Liotta, Francesco; Palma, Raffaele De; Maggi, Enrico; Romagnani, Sergio; Annunziato, Francesco

doi:10.1002/art.30332

Cited by 202 publications

(260 citation statements)

References 43 publications

(48 reference statements)

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“…The Th17 cells shared clonal ancestry with CD161+ Th17/Th1 and CD161+ Th1 cells present in the SF, and circulating Th17 cells from healthy subjects demonstrated Th17 to Th1 plasticity in vitro in the presence of SF from JIA patients, which could be blocked by IL-12-neutralization. More importantly, the numbers of CD4+ CD161+ cells, particularly the Th17/ Th1 cells, in SF of JIA patients positively correlated with levels of erythrocyte sedimentation rate and C-reactive protein (37). Taken together, these findings support the hypothesis that Th17-derived Th17/Th1 and Th1 cells, rather than Th17 cells, play a critical role in disease activity.…”

Section: The Discovery Of Th17 Cells In Mice and Humanssupporting

confidence: 67%

“…Likewise, we have found an accumulation of CD4+ CD161+ T cells able to produce IFN-c (Th1), or both IFN-c and IL-17A (Th17/Th1), but not IL-17A alone (Th17), in the synovial fluid (SF) of children with oligoarticular juvenile idiopathic arthritis (JIA) (37). The Th17 cells shared clonal ancestry with CD161+ Th17/Th1 and CD161+ Th1 cells present in the SF, and circulating Th17 cells from healthy subjects demonstrated Th17 to Th1 plasticity in vitro in the presence of SF from JIA patients, which could be blocked by IL-12-neutralization.…”

Section: The Discovery Of Th17 Cells In Mice and Humansmentioning

confidence: 98%

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Th17 cells: new players in asthma pathogenesis

Cosmi

Liotta

Maggi

et al. 2011

Allergy

280

195

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CD4+ T effector lymphocytes are distinguished in different subsets on the basis of their patterns of cytokine secretion. Th1 cells, thank to IFN-c production, are responsible for cell-mediated immunity against intracellular pathogens, Th2 cells, through the production of IL-4, provide some degree of protection against helminthes, and Th17 cells, via IL-17, promote neutrophils recruitment for the clearance of bacteria and fungi. However, beyond their protective role, these T-helper subsets can also be involved in the pathogenesis of several inflammatory diseases. Asthma is an inflammatory disease characterized by different clinical phenotypes. Allergic asthma is the result of an inflammatory process driven by allergen-specific Th2 lymphocytes, whereas Th17 cells are mainly involved in those forms of asthma, where neutrophils more than eosinophils, contribute to the inflammation. The identification in allergic asthma of Th17/Th2 cells, able to produce both IL-4 and IL-17, is in keeping with the observation that different clinical phenotypes can coexist in the same patient. In conclusion, a picture in which different T-cell subpopulations are active in different phase of bronchial asthma is emerging, and the wide spectrum of clinical phenotypes is probably the expression of different cellular characters playing a role in lung inflammation.

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Section: The Discovery Of Th17 Cells In Mice and Humanssupporting

confidence: 67%

Section: The Discovery Of Th17 Cells In Mice and Humansmentioning

confidence: 98%

Th17 cells: new players in asthma pathogenesis

Cosmi

Liotta

Maggi

et al. 2011

Allergy

280

195

View full text Add to dashboard Cite

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“…Th17 cells have important roles in autoimmune and chronic inflammatory disorders, such as rheumatoid arthritis (31)(32)(33). The control of the Th17 responses has already yielded successful results in a clinical trial with rheumatoid arthritis patients (29).…”

Section: Resultsmentioning

confidence: 99%

Molecular Basis for LLT1 Protein Recognition by Human CD161 Protein (NKRP1A/KLRB1)

Kamishikiryo

Fukuhara

Okabe

et al. 2011

Journal of Biological Chemistry

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“…The C-type lectin receptor CD161 and the CC chemokine receptor CCR6 are considered the best phenotypic cell surface markers for human IL-17-producing T cells to date, and Th17 cells have been described by multiple groups to be selectively located within the CD161 + subset and linked to CCR6 expression (6,(22)(23)(24)(25). We thus compared the coexpression of CD26 and CD161 or CCR6 on CD4 + T cells and, specifically, Th17 cells.…”

Section: The Cd26mentioning

confidence: 99%

Human Th17 Cells Express High Levels of Enzymatically Active Dipeptidylpeptidase IV (CD26)

Bengsch

Seigel

Flecken

et al. 2012

The Journal of Immunology

150

161

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Dipeptidylpeptidase IV (CD26) is a multifunctional ectoenzyme involved in T cell activation that has been implicated in autoimmune pathophysiology. Because IL-17–producing CD4+ T cells (Th17 cells) are important mediators of autoimmune disease, we analyzed the expression of CD26 and its enzymatic function on human Th17 cells. Analysis of CD26 expression on different CD4+ T helper subsets showed that CD26 expression is highest on CD4+ T cells producing type 17 cytokines (e.g., IL-22, IL-17, GM-CSF, or TNF) compared with Th1, Th2, and regulatory T cells. Phenotypic analysis revealed that CD26++CD4+ T cells express the type 17 differentiation molecules CD161, CCR6, lL-23R, and retinoic acid-related orphan receptor-γt. Furthermore, sorted CD26++CD4+ T cells contain >90–98% of Th17 cells, indicating that CD26++ T cells harbor the Th17 lineage. A comparison with CD161 and CCR6 indicated that analysis of CD26 coexpression may improve the phenotypic characterization of Th17 cells. Of note, CD26++ Th17 cells are enriched in the inflamed tissue of patients with hepatitis and inflammatory bowel disease. Functional analysis in migration assays revealed that CD26 expressed on Th17 cells is enzymatically active. Indeed, CD26 negatively regulates the chemotactic CD4+ T cell response to the inflammatory chemokines CXCL9–12 that can be restored by pharmacological blockade of the enzymatic center of CD26. In summary, these results strongly suggest that CD26 may contribute to the orchestration of the immune response by Th17 cells in human inflammatory diseases. They also suggest that the phenotypic analysis of Th17 cells may be facilitated by determination of CD26 expression.

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Evidence of the transient nature of the Th17 phenotype of CD4+CD161+ T cells in the synovial fluid of patients with juvenile idiopathic arthritis

Cited by 202 publications

References 43 publications

Th17 cells: new players in asthma pathogenesis

Th17 cells: new players in asthma pathogenesis

Molecular Basis for LLT1 Protein Recognition by Human CD161 Protein (NKRP1A/KLRB1)

Human Th17 Cells Express High Levels of Enzymatically Active Dipeptidylpeptidase IV (CD26)

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